The main topics of the conference included: human iPS cells with emphasis on the clinical applications, tissue engineering and regenerative medicine. The first session of the meeting was chaired by Dr.

Christopher Duntsch's insight:

This is a good review and report of what is trending now in tissue engineering. The push early was therapies with cells derived from mature tissue, or tissue sections from mature tissues, that were transferred into a degenerated, damaged, or diseased tissue with the hope of some sort of therapeutic or regenerative healing or reversal of the disease process. There are a few exceptions, but this approach never worked well in vitro, in vivo in animals, much less in the clinical studies that followed. The shift to stem cell technologies was a paradigm shift and in the right direction, but still there has not been a great deal of success using stem cell therapies in isolation. There are rare exceptions as always (HSCs and BM transplants).

Years ago and even more so recently, the definition of tissue engineering, has changed significantly. There are now so called core components, and is agreed by most that the ‘sum of the parts are greater than the "whole". In the most basic sense, I would think it could be simplified to 1) a stem cell product or therapeutic 2) support factors of many types … growth factors, nutrients, supplements, etc., 3) a 3D scaffold of some type.

This article keys in on successes that have begun to be seen in the scientific literature as of late. Namely, that in addition to the above, one must consider the impact of stem cells as before, but also of progenitor cells, changes in phenotype that are smart and strategic and also in line with fundamental biology, and for lack of a better word for it, developmental biology. In any normal solid organ, there is a rare but immortal adult stem cell population, and that stem cell is quiescent most often, at least in a healthy state. However, inflammation and other molecular events that occur with disease and damage and degeneration can push quiescent stem cells to asymmetrically give off early progenitors. These are the machines of tissue development, as they are of effective regenerative medicine.

As early progenitors mature, they change in phenotype, lose stem cell phenotypy, and gain terminal lineage phenotypy. Eventually, as cells proliferate and migrate and fill a tissue niche, they crowd and mature and secrete ECM and enzymes. EC enzymes such as MMPs, and Cell surface adhesion molecules and receptors, interact with ECM such as proteoglycans and glycosaminoglycans, and eventually cells fix in space in time, communicate locally, and organize. The result is prefabricated tissue that is the infrastructure and architectural pathway to the end goal.. As this remodels continuously, the cell and tissue and the structure / architecture remodels and continues to mature and evolve. Ideally, a relatively regenerated tissue with structure, order, and function, is left where once there was damaged or nonfunctional tissue.

The point of the above is that the rough approximation of developmental biology in vitro in not just important but required for successful tissue engineering. And this requires more than the three core components mentioned. Without more detail, it is enough to simply make these descriptive comments. Despite the lack of detail for what follows, it is fairly logical to assume that an in vitro developmental biology influence is indeed a key fourth core for tissue engineering.

Principles of Tissue Engineering with the following four core components.

4 A series of key steps, protocols, manipulations that provide a developmental nature or influence to the biological device prior to transplant into the animal.

In summary, a definition of an ideal tissue engineering product: A stem cell therapeutic, seeded into a tissue engineering complex in vitro, supplemented with ECM, GFs, supplements, etc, which, after methods and protocols are carried forward correctly, results in a comprehensive biological device or structure that has the following components:

2 an early progenitor fraction rapidly dividing and migrating throughout the structure, and,

3 a small late progenitor fraction that is beginning to some degree to mature to the lineage of the cells needed for the tissue treated.

The importance is that the biological device used for tissue engineering is: primed genetically, epigenetically, and with respect to its cell and molecular phenotype; phenotypically more effective at integrating / assimilating into the target tissue, and immediately starts to grow, mature, change, and regenerate the tissue defect or replace / treat / supplement a diseased or degenerated tissue. Makes sense.

Foundation building, a valid, solid, and smart approach to building a genomic, epigenetic / TF factor and gene target cohesive model, stem cell and progenitor and cell biology paradigm, cell proliferation, migration, maturation, differentiation biologic, and all the intracellular and extracellular machinery that take a chaotic mass of cells and polymers and matrix and the like, and pull it together into ever increasing layers of organization best known as tissue fabrication.

This occurs as a first step to a complex end. Biomechanical forces, ECM and Cell Cell contact, polymer matrix biology, morphogens, and neighboring cells and tissues, all are a player in this. From pre-tissue a tissue forms, but not fully mature, certainly not functional, until much more occurs Tissue remodeling, and structure function development of the first product of the effort described above are both needed and strategically part of the biology.

Recreating said modeling as above, for cartilage development, whether static, structural, dynamic, or functional, will be an equally difficult and equally important first step for stem cell biology and cell biology of cartilage development into first tissue then structure and function. A first step nonetheless, but a milestone that cannot be bypassed. That being a developmental biology model, integration of stem cell biology, and extrapolating from cells and molecular machines, to a full understanding at all levels what transpired to create the tissue or organ in question with its architecture, function, and purpose.

This may sound a like a lot to do about nothing, but while this is a foundation for next gen therapeutics, the translation from in vivo foundational studies and knowledge derived therein, to a stem cell based tissue engineered regenerative product of real substance, safety, efficacy practicality, etc, once done well, is the single biggest challenge the stem cell biologist and tissue engineering scientist face in every aspect of animal biology at every level, in healthy and disease, in young and in old.

And why might that be. The answer why does not need to be sought long to be given. It is a simple matter to observe that a true in vitro 3D complex functional stem cell based biologic device with matrix biology and tissue engineering integrated into the system, and at the same time the overlay of cell biology paradigms that serve to lead the way for all yet do not exist until understood, architected, and implemented by the scientist.

Only for these UCLA researchers and others now and that follow, they do not have the advantage of God's infinite science, nor that of the uncountable mistakes that occurred as building blocks of randomness came together every 600th time they interacted, and over 4 billion years, eventually created unimaginable intelligent design. Indeed, the challenge is taking what has been learned, and what is known as well, and combining that with technologies and biomaterials from the tissue of interest, from surrogate molecules and matrix biology (both living, synthetic and inert), and combining all into a 3D structure static and dynamical properties, architecture that gives function by design, and as above, the overlay of a near invisible yet all powerful cell biology protocol set that is the driver of the machine.

Compared to the foundational and translational studies that are so complex, slow to develop, and slow to translate, I think we will see a rapid acceleration in scientific and medical breakthroughs as the milestones of the first two phases slowly are reached. However, this is more likely if there efforts parallel the scientific methods and a team effort for all those academic and commercial, scientific and clinical. If the intent and drive is there, and the research is done well, then the final key biologic is that of the in vitro transition phase. Meaning integrating the biology of the biotechnology created into the human condition for disease or other clinical purpose should be similar to the inherent self driven and all knowing developmental biology of the foundation.

The nobel prize medicine here is in two areas, the early discovery science of the foundation, and all aspects of in vitro translation to human application. That is something most don't quite grasp in the current day.

BioNews Texas New Hope For COPD Sufferers In Lung Regeneration BioNews Texas After publishing four articles in the leading bioengineering journal Biomaterials, and two March 2014 articles with postdoctoral fellow in medicine Darcy Wagner, PhD.,...

Christopher Duntsch's insight:

Momentum Gaining for Stem Cell Based Therapies, Tissue Engineering, and Regenerative Medicine for the Treatment of Lung Disease

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